The U.S. Food and Drug Administration (FDA) today approved gemtuzumab ozogamicin (Mylotarg) for the treatment of adults with newly diagnosed acute myeloid leukemia (AML) whose tumors express the CD33 antigen. The drug was also approved for the treatment of patients aged 2 years and older with relapsed or refractory CD33-positive AML.

Gemtuzumab ozogamicin originally received accelerated approval in May 2000 as a stand-alone treatment for older patients with CD33-positive AML who had experienced a relapse. The drug was voluntarily withdrawn from the market after subsequent confirmatory trials failed to verify clinical benefit and demonstrated safety concerns, including a high number of early deaths. Today’s approval includes a lower recommended dose, a different schedule in combination with chemotherapy or on its own, and a new patient population.

“We are approving Mylotarg after a careful review of the new dosing regimen, which has shown that the benefits of this treatment outweigh the risk,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Mylotarg’s history underscores the importance of examining alternative dosing, scheduling, and administration of therapies for patients with cancer, especially in those who may be most vulnerable to the side effects of treatment.”

Pivotal Trials

The safety and efficacy of gemtuzumab ozogamicin in combination with chemotherapy for adults were studied in a trial of 271 patients with newly diagnosed CD33-positive AML who were randomized to receive gemtuzumab ozogamicin in combination with daunorubicin and cytarabine or to receive daunorubicin and cytarabine without gemtuzumab ozogamicin. The trial measured event-free survival. Patients who received gemtuzumab ozogamicin in combination with chemotherapy went longer without complications than those who received chemotherapy alone (median event-free survival = 17.3 vs 9.5 months).

The safety and efficacy of gemtuzumab ozogamicin as a stand-alone treatment were studied in two separate trials. The first trial included 237 patients with newly diagnosed AML who could not tolerate or chose not to receive intensive chemotherapy. Patients were randomized to receive treatment with gemtuzumab ozogamicin or best supportive care. The trial measured overall survival. Patients who received gemtuzumab ozogamicin survived longer than those who received only best supportive care (median overall survival = 4.9 vs 3.6 months).

The second trial was a single-arm study that included 57 patients with CD33-positive AML who had experienced one relapse of disease. Patients received a single course of gemtuzumab ozogamicin. The trial measured how many patients achieved a complete remission. Following treatment with gemtuzumab ozogamicin, 26% of patients achieved a complete remission that lasted a median 11.6 months.

Toxicity Profile

Common side effects of gemtuzumab ozogamicin include pyrexia, nausea, infection, vomiting, bleeding, thrombocytopenia, stomatitis, constipation, rash, headache, elevated liver function tests, and neutropenia. Severe side effects of gemtuzumab ozogamicin include low blood counts, infections, liver damage, hepatic veno-occlusive disease, infusion-related reactions, and hemorrhage. Women who are pregnant or breastfeeding should not take gemtuzumab ozogamicin. Patients with hypersensitivity to the drug or any component of its formulation should not use gemtuzumab ozogamicin.

Prescribing information for the drug includes a boxed warning that severe or fatal liver damage, including veno-occlusive disease or sinusoidal obstruction syndrome, occurred in some patients who took gemtuzumab ozogamicin.

Gemtuzumab ozogamicin received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.

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